27,720 results match your criteria inhibitors anticancer

AKR1C3 decreased CML sensitivity to Imatinib in bone marrow microenvironment via dysregulation of miR-379-5p.

Cell Signal 2021 May 10:110038. Epub 2021 May 10.

Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China. Electronic address:

Background: Drug resistance is an important cause of death for most patients with chronic myeloid leukemia (CML). The bone marrow microenvironment is believed to be mainly responsible for resistance to BCR-ABL tyrosine kinase inhibitors. The mechanism involved, however, is still unclear. Read More

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New isolate from Salvinia molesta with antioxidant and urease inhibitory activity.

Drug Dev Res 2021 May 13. Epub 2021 May 13.

Drug Design Development Research Group, Department of Chemistry, Universiti Malaya, Kuala Lumpur, Malaysia.

Urease plays a significant role in the pathogenesis of urolithiasis pyelonephritis, urinary catheter encrustation, hepatic coma, hepatic encephalopathy, and peptic acid duodenal ulcers. Salvinia molesta was explored to identify new bioactive compounds with particular emphasis on urease inhibitors. The aqueous methanol extract was fractionated using solvents of increasing polarity. Read More

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DNA Damage Repair Inhibitor for Breast Cancer Treatment.

Adv Exp Med Biol 2021 ;1187:159-179

Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.

Cancer has been defined as a genetic disorder caused by the accumulation of genetic alterations, which result from various internal and external DNA damage that is left unrepaired. One of the main characteristics of cancer is a partial loss of DNA damage repair (DDR) pathway, resulting in increased DNA damage levels and replication stress. DDR inhibitors have been suggested as a new anticancer strategy, under the concept of synthetic lethality. Read More

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January 2021

Acute toxicity analysis of an inhibitor of BCL2, Disarib, in rats.

Sci Rep 2021 May 11;11(1):9982. Epub 2021 May 11.

Institute of Bioinformatics and Applied Biotechnology, Electronics City, Bangalore, 560100, India.

Apoptosis or programmed cell death is a highly regulated process, which eliminates unwanted and damaged cells. Inhibition of apoptosis is a hallmark of cancer cells. BCL2 family proteins are known to play a vital role in the regulation of apoptosis. Read More

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Structure-Guided Design of the First Noncovalent Small-Molecule Inhibitor of CRM1.

J Med Chem 2021 May 11. Epub 2021 May 11.

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, Sichuan University and Collaborative Innovation Centre of Biotherapy, Chengdu 610041, China.

Nuclear export factor chromosome region maintenance 1 (CRM1) is an attractive anticancer and antiviral drug target that spurred several research efforts to develop its inhibitor. Noncovalent CRM1 inhibitors are desirable, but none is reported to date. Here, we present the crystal structure of yeast CRM1 in complex with S109, a substructure of CBS9106 (under clinical test). Read More

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QSAR analysis of 3-pyrimidin-4-yl-oxazolidin-2-one derivatives isocitrate dehydrogenase inhibitors using Topomer CoMFA and HQSAR methods.

Mol Divers 2021 May 11. Epub 2021 May 11.

College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an, 710021, China.

A series of mIDH1 inhibitors derived from 3-pyrimidine-4-oxazolidin-2-ketone derivatives were studied by QSAR model to explore the key factors that inhibit mIDH1 activity. The generated model was cross-verified and non-cross-verified by Topomer CoMFA and HQSAR methods; the independent test set was verified by PLS method; the Topomer search technology was used for virtual screening and molecular design; and the Surflex-Dock method and ADMET technology were used for molecular docking, pharmacology and toxicity prediction of the designed drug molecules. The Topomer CoMFA and HQSAR cross-validation coefficients q are 0. Read More

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The Role of Gut Microbiota in Modulating Tumor Growth and Anticancer Agent Efficacy.

Mol Cells 2021 04 23. Epub 2021 Apr 23.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

An increasing number of studies have revealed an interaction between gut microbiota and tumors. The enrichment of specific bacteria strains in the intestines has been found to modulate tumor growth and influence the mechanisms of tumor treatment. Various bacteria are involved in modulating the effects of chemotherapeutic drugs currently used to treat patients with cancer, and they affect not only gastrointestinal tract tumors but also distant organ tumors. Read More

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Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.

Bioorg Med Chem 2021 May 1;40:116182. Epub 2021 May 1.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

The ubiquitin proteasome pathway (UPP) plays a critical role in the maintenance of cell homeostasis and the development of diseases, such as cancer and neurodegenerative disease. A series of novel tripeptide propylene oxide compounds as proteasome inhibitors were designed, synthesized and biologically investigated in this manuscript. The enzymatic activities of final compounds against 20S human proteasome were investigated and structure-activity relationship (SAR) was summarized. Read More

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Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent update on inhibitor design and clinical trials (2016-2020).

Expert Opin Ther Pat 2021 May 10. Epub 2021 May 10.

DSC 362, Department of Chemistry, The University of Nebraska at Omaha, 6001 Dodge Street, Omaha, Nebraska 68182, USA.

Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in regulating cell growth and proliferation and thus have been considered as effective anticancer drug targets. Many PI3K inhibitors have been developed and progressed to various stages of clinical trials and some even have been approved in recent years by the regulatory agency as anticancer treatment. In this review, we discuss the drug design and clinical development of PI3K inhibitors in the past four years. Read More

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Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential.

Nat Prod Res 2021 May 10:1-10. Epub 2021 May 10.

Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.

The chalcone derivatives of 20-oxo-lupanes have been synthesised and screened for some types of biological activity. Ozonolysis of lupanes afforded 20-oxo-derivatives with the following condensation using different aromatic aldehydes by Claisen‒Schmidt reaction to the target compounds. The configuration of 19-[3-(pyridin-3-yl)-prop-2-en-1-one]-fragment was established by X-ray analysis. Read More

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Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells.

Bioorg Med Chem 2021 Apr 30;40:116187. Epub 2021 Apr 30.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Carboxylesterase 2 (CES2) is one of the most important Phase I drug metabolizing enzymes in the carboxylesterase family. It plays crucial roles in the bioavailability of oral ester prodrugs and the therapeutic effect of some anticancer drugs such as irinotecan (CPT11) and capecitabine. In addition to the well-known roles of CES2 in xenobiotic metabolism, the enzyme also participates in endogenous metabolism and the production of lipids. Read More

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Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Bioorg Med Chem Lett 2021 May 11;43:128095. Epub 2021 May 11.

School of Basic Medical Sciences, Zhengzhou University Zhengzhou 450001, China. Electronic address:

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. Read More

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Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents.

Bioorg Chem 2021 Apr 27;112:104947. Epub 2021 Apr 27.

Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Riyadh, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. Electronic address:

Vascular endothelial growth factor-2 (VEGFR-2) is considered one of the most important factors in tumor angiogenesis, and consequently a number of anticancer therapeutics have been developed to inhibit VEGFR-2 signaling. Accordingly, eighteen derivatives of thieno[2,3-d]pyrimidines having structural characteristics similar to VEGFR-2 inhibitors were designed and synthesized. Anticancer activities of the new derivatives were assessed against three human cancer cell lines (HCT-116, HepG2, and MCF-7) using MTT. Read More

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Specific inhibition of oncogenic RAS using cell-permeable RAS-binding domains.

Cell Chem Biol 2021 May 4. Epub 2021 May 4.

United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan. Electronic address:

Oncogenic RAS proteins, common oncogenic drivers in many human cancers, have been refractory to conventional small-molecule and macromolecule inhibitors due to their intracellular localization and the lack of druggable pockets. Here, we present a feasible strategy for designing RAS inhibitors that involves intracellular delivery of RAS-binding domain (RBD), a nanomolar-affinity specific ligand of RAS. Screening of 51 different combinations of RBD and cell-permeable peptides has identified Pen-cRaf-v1 as a cell-permeable pan-RAS inhibitor capable of targeting both G12C and non-G12C RAS mutants. Read More

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TRAIL-Armed ER Nanosomes Induce Drastically Enhanced Apoptosis in Resistant Tumor in Combination with the Antagonist of IAPs (AZD5582).

Adv Healthc Mater 2021 May 8:e2100030. Epub 2021 May 8.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 51006, China.

Although mesenchymal stem cells (MSCs) can be engineered to deliver the TNF-related apoptosis-inducing ligand (TRAIL) as an effective anticancer therapy, the clinical application is hampered by the costly manufacturing of therapeutic MSCs. Therefore, it is needed to find an alternative cell-free therapy. In this study, TRAIL-armed endoplasmic reticulum (ER)-derived nanosomes (ERN-T) are successfully prepared with an average size of 70. Read More

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Novel 4-(piperazin-1-yl)quinolin-2(1H)-one bearing thiazoles with antiproliferative activity through VEGFR-2-TK inhibition.

Bioorg Med Chem 2021 Apr 22;40:116168. Epub 2021 Apr 22.

Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt; Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Deraya University, New Minia, Minia, Egypt. Electronic address:

A new series of 2-(4-(2-oxo-1,2-dihydroquinolin-4-yl)piperazin-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivatives were synthesized and evaluated for anticancer activity. All target compounds showed anticancer activity higher than that of their 2-oxo-4-piperazinyl-1,2-dihydroquinolin-2(1H)-one precursors. Multidose testing of target compounds was performed against breast cancer T-47D cell line. Read More

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The biology of combination immunotherapy in recurrent metastatic head and neck cancer.

Int J Biochem Cell Biol 2021 May 4;136:106002. Epub 2021 May 4.

Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China. Electronic address:

Preclinical data suggest that head and neck cancer is an intrinsically immunosuppressive disease with abnormal inflammatory components in the tumor microenvironment. The development of immune checkpoint inhibitors, which are monoclonal antibodies capable of inhibiting immune suppressive signals to prime anticancer immunity, has revolutionized the therapeutic landscape in recurrent/metastatic head and neck cancer. However, patients with head and neck cancer present primary resistance to immunotherapy. Read More

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Complement C3a activates osteoclasts by regulating the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.

Cancer Biol Med 2021 May 7. Epub 2021 May 7.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China.

Objective: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease. However, the mechanism of C3a/C4a in osteoclasts MM patients remains unclear. Read More

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Detection of exon 14 skipping mutations in non-small cell lung cancer: overview and community perspective.

Expert Rev Anticancer Ther 2021 May 7. Epub 2021 May 7.

Department of Pathology, Saint Luke's Health System of Kansas City, MAWD Pathology Group, Lenexa, Kansas, USA.

: Non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer diagnoses in the United States, has many known driver mutations, including exon 14 skipping mutation (ex14). The detection of oncogenic driver mutations in NSCLC and the development of drugs to target these alterations, including ex14, has created the need for accurate and reliable testing, of which next-generation sequencing (NGS) is the gold standard. However, detection of ex14 in patients with NSCLC can be challenging due to the complex biology of ex14 and the abilities of different NGS platforms to detect ex14. Read More

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Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer.

Eur J Med Chem 2021 Apr 25;220:113453. Epub 2021 Apr 25.

School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, China. Electronic address:

LSD1 and HDAC are physical and functional related to each other in various human cancers and simultaneous pharmacological inhibition of LSD1 and HDAC exerts synergistic anti-cancer effects. In this work, a series of novel LSD1/HDAC bifunctional inhibitors with a styrylpyridine skeleton were designed and synthesized based on our previously reported LSD1 inhibitors. The representative compounds 5d and 5m showed potent activity against LSD1 and HDAC at both molecular and cellular level and displayed high selectivity against MAO-A/B. Read More

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Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance.

Front Pharmacol 2021 19;12:648407. Epub 2021 Apr 19.

State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.

Multiple drug resistance (MDR), referring to the resistance of cancer cells to a broad spectrum of structurally and mechanistically unrelated drugs across membranes, severely impairs the response to chemotherapy and leads to chemotherapy failure. Overexpression of ATP binding cassette (ABC) transporters is a major contributing factor resulting in MDR, which can recognize and mediate the efflux of diverse drugs from cancer cells, thereby decreasing intracellular drug concentration. Therefore, modulators of ABC transporter could be used in combination with standard chemotherapeutic anticancer drugs to augment the therapeutic efficacy. Read More

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Prognostic Significance of Gene Mutation in Patients With EGFR Mutated Non-small Cell Lung Cancer Who Received Best Supportive Care Alone.

Anticancer Res 2021 May;41(5):2661-2667

Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

Background/aim: The significance of epidermal growth factor receptor (EGFR) mutation in untreated patients with non-small cell lung cancer (NSCLC) remains uncertain. We aimed to determine the significance of EGFR mutation in patients who received best supportive care (BSC) alone, and compare the outcomes of only EGFR- tyrosine kinase inhibitors (TKI)-treated vs. BSC patients. Read More

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Comparison of Chemotherapeutic Regimens Frequently Used in Metastatic Non-squamous NSCLC Treatment.

Anticancer Res 2021 May;41(5):2597-2603

Department of Pneumology and Phthisiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic

Background/aim: Platinum-based chemotherapy with pemetrexed or paclitaxel/bevacizumab are regimens used in combination with checkpoint inhibitors in non-squamous non-small cell lung cancer (NSCLC) treatment. We conducted a real-world study to compare the outcomes of these chemotherapeutic regimens.

Patients And Methods: We investigated 1,534 patients with advanced non-squamous NSCLC treated with platin/pemetrexed (n=1212) or platin/paclitaxel/bevacizumab (n=322) in 9 cancer centres in the Czech Republic. Read More

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Prognosis of Patients With Interstitial Lung Disease Induced by Different Pharmacological Types of Anticancer Drugs.

Anticancer Res 2021 May;41(5):2563-2568

Department of Clinical Pharmacy, Fujita Health University School of Medicine, Toyoake, Japan.

Background/aim: The aim of this study was to evaluate the effect of drug-induced interstitial lung disease (DILD) on treatment outcomes by comparing the mortality of patients with DILD induced by different pharmacological types of anticancer drugs.

Patients And Methods: Japanese patients with lung cancer who had received chemotherapy at Fujita Health University Hospital were enrolled. The primary outcome was the short-term mortality rate from the administration of chemotherapy that might have caused DILD. Read More

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A TGFβ Signaling Inhibitor, SB431542, Inhibits Reovirus-mediated Lysis of Human Hepatocellular Carcinoma Cells in a TGFβ-independent Manner.

Anticancer Res 2021 May;41(5):2431-2440

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan;

Background/aim: Oncolytic reovirus, which is a non-enveloped virus possessing a 10-segmented double-stranded RNA genome, has been anticipated as a novel class of antitumor agent. Hepatocellular carcinoma (HCC) is considered to be a target suitable for reovirus-mediated virotherapy. Transforming growth factor (TGF)-β plays an important role in the pathogenesis of HCC. Read More

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PARP1 Is Overexpressed in Hematological Malignant Cell Lines: A Framework for Experimental Oncology.

Anticancer Res 2021 May;41(5):2397-2402

Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.

Background/aim: Experimental oncology commonly uses cells as oncological models, providing a framework for the testing of drugs, and investigation of cytotoxicity, mutagenesis and carcinogenesis. Investigations into poly-ADP-ribose polymerase 1 (PARP1) inhibition have become ever more relevant due to its approval as a therapeutic option for tumors with BRCA1/2 DNA repair-associated mutation and the seemingly high PARP expression levels in some tumor subtypes. In this study, we aimed to determine PARP1 gene expression of different hematological cancer-derived cell lineages and compare them to that of normal cell lines. Read More

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Estrogen Receptor β Is Involved in Acquired Resistance to EGFR-tyrosine Kinase Inhibitors in Lung Cancer.

Anticancer Res 2021 May;41(5):2371-2381

Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan;

Background/aim: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has posed serious clinical problems in the treatment of lung adenocarcinoma (LADC) patients harboring relevant EGFR mutations. In this study, we explored the role of estrogen receptor β (ERβ) in the development of acquired resistance to EGFR-TKIs in human LADC.

Materials And Methods: First, the role of ERβ in erlotinib resistance of LADC cell lines (PC9/ER) was examined. Read More

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Retinoids Decrease Soluble MICA Concentration by Inhibiting the Enzymatic Activity of ADAM9 and ADAM10.

Anticancer Res 2021 May;41(5):2307-2320

Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

Background/aim: The association between MHC class I polypeptide-related sequence A (MICA) and hepatocellular carcinoma (HCC) development was identified in our previous genome-wide association study. Decreasing soluble MICA (sMICA) through MICA sheddases suppression facilitates natural killer (NK) cell-mediated cytotoxicity. The expression of ADAM9 in HCC has been correlated with poor prognosis, and our recent study showed that its suppression contributes to cancer elimination by decreasing sMICA. Read More

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Structure-activity Relationship of Indomethacin Derivatives as IDO1 Inhibitors.

Anticancer Res 2021 May;41(5):2287-2296

School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.

Background/aim: Indoleamine 2,3-dioxygenase (IDO) is regarded as an important molecular target for cancer immune therapy. This study aimed to examine the IDO1 inhibitory activity of newly synthesized indomethacin derivatives to develop an IDO1 inhibitor.

Materials And Methods: The inhibitory effects of indole-containing compounds against recombinant human IDO1 (rhIDO1) were evaluated. Read More

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Synergistic Effect of Bazedoxifene and PARP Inhibitor in the Treatment of Ovarian Cancer Regardless of BRCA Mutation.

Anticancer Res 2021 May;41(5):2277-2286

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, U.S.A.

Background/aim: Poly (ADP-ribose) polymerase inhibitors (PARPis) are one of the targeted therapies proven to treat breast cancer gene (BRCA)-mutant ovarian cancer. Because most ovarian cancers are BRCA wild-type, it is necessary to extend the usage of PARPis. In the present study, we combined the PARPi, talazoparib, and the IL-6 inhibitor, bazedoxifene, for the treatment of human ovarian cancer cells. Read More

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